Biology subjects

Peterson, J. G.

Publications and source records attributed to Peterson, J. G..

3 recordsLinked to original sources

bioRxiv2026

Systemic diazepam alters local hippocampal CA1 circuits and differentially affects entorhinal and CA3 inputs

The GABAA positive allosteric modulator diazepam is taken systemically by millions of people daily. GABAA signaling is essential for hippocampal circuit function, but the effects of systemic diazepam on hippocampal information processing during behavior has not been studied. To answer this question, large neural ensembles were recorded from rats running a linear track under systemic diazepam administration. A cross-correlation of spiking activity revealed significantly increased inhibition from interneurons, aligned with the timescale of GABAA, suggesting a direct effect on local circuits. Local field potentials (LFP) showed an increase in theta and lo-gamma (30-50 Hz) power but a decrease in hi-gamma (80-120 Hz) power. We also found decreased amplitude and rate of sharp wave ripple (SWR) events and a reduction of firing rate and proportion of cells recruited to the SWRs. An autocorrelation of single-cell spike trains revealed a decrease and shift from shorter to longer timescales, aligning differently with theta frequencies. Phase coupling measurements showed decreased cellular coupling to theta and increased coupling to lo-gamma and hi-gamma. Finally, entropy of decoding along the track was increased, suggesting less precise spatial representations under diazepam. These changes suggest mechanisms that would likely disrupt hippocampal memory storage and consolidation processes under systemic diazepam.

neuroscience↗

bioRxiv2022

A Genomically and Clinically Annotated Patient Derived Xenograft (PDX) Resource for Preclinical Research in Non-Small Cell Lung Cancer

Patient-derived xenograft models (PDXs) are an effective preclinical in vivo platform for testing the efficacy of novel drug and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathological features, mutational profiles, gene expression, and copy number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors of the same tumor type from The Cancer Genome Atlas (TCGA) and to previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted tumors. Treatment studies performed for a subset of the models recapitulated the responses expected based on the observed genomic profiles. SignificanceThe collection of lung cancer Patient Derived Xenograft (PDX) models maintained at The Jackson Laboratory retain both the histologic features and treatment-relevant genomic alterations observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents. The models serve as a valuable preclinical platform for translational cancer research. Information and data for the models are freely available from the Mouse Models of Human Cancer database (MMHCdb, http://tumor.informatics.jax.org/mtbwi/pdxSearch.do).

cancer biology↗

bioRxiv2021

Identification of Arhgef12 and Prkci as Genetic Modifiers of Retinal Dysplasia in the Crb1rd8 Mouse Model

Mutations in the apicobasal polarity gene CRB1 lead to diverse retinal diseases, such as Leber congenital amaurosis, cone-rod dystrophy, retinitis pigmentosa (with and without Coats-like vasculopathy), foveal retinoschisis, macular dystrophy, and pigmented paravenous chorioretinal atrophy. Limited correlation between disease phenotypes and CRB1 alleles, and evidence that patients sharing the same alleles often present with different disease features, suggest that genetic modifiers contribute to clinical variation. Similarly, the retinal phenotype of mice bearing the Crb1 retinal degeneration 8 (rd8) allele varies with genetic background. Here, we initiated a sensitized chemical mutagenesis screen in B6.Cg-Crb1rd8/Pjn, a strain with a mild clinical presentation, to identify genetic modifiers that cause a more severe disease phenotype. Two models from this screen, Tvrm266 and Tvrm323, exhibited increased retinal dysplasia. Genetic mapping with high-throughput exome and candidate-gene sequencing identified causative mutations in Arhgef12 and Prkci, respectively. Epistasis analysis of both strains indicated that the increased dysplastic phenotype required homozygosity of the Crb1rd8 allele. Retinal dysplastic lesions in Tvrm266 mice were smaller and caused less photoreceptor degeneration than those in Tvrm323 mice, which developed an early, large diffuse lesion phenotype. In both models at one month of age, Muller glia and microglia mislocalization at dysplastic lesions was similar to that in B6.Cg-Crb1rd8/Pjn mice, while photoreceptor cell mislocalization was more extensive. External limiting membrane disruption was comparable in Tvrm266 and B6.Cg- Crb1rd8/Pjn mice but milder in Tvrm323 mice. Immunohistological analysis of mice at postnatal day 0 indicated a normal distribution of mitotic cells in Tvrm266 and Tvrm323 mice, suggesting normal early development. Aberrant electroretinography responses were observed in both models but functional decline was significant only in Tvrm323 mice. These results identify Arhgef12 and Prkci as modifier genes that differentially shape Crb1-associated retinal disease, which may be relevant to understanding clinical variability and underlying disease mechanisms.

genetics↗